PROJECT SUMMARY/ABSTRACT This K01 Mentored Research Scientist Development Award proposal seeks to provide Dr. David Chester with the training and research experiences necessary to advance his career goal of becoming an independent alcohol investigator. He seeks this career goal in order to better understand and intervene upon the biological bases (i.e., genetic risk factors, neural mechanisms) of alcohol-influenced aggression. The activities in this proposal will build upon Dr. Chester's existing skillset in the psychological and neural bases of aggressive behavior. Training plan: Dr. Chester seeks training in advanced genetic techniques and alcohol misuse phenotypes, which will be achieved through a structured training plan that consists of regular meetings with mentors, two external laboratory rotations, coursework and a workshop in statistical genetics, directed readings, and two laboratory rotations. Dr. Chester's training plan leverages the outstanding research and educational environment at Virginia Commonwealth University (VCU) with a team of renowned experts as mentors. His primary mentor is Dr. Danielle Dick (an expert in genetic risk factors for alcohol misuse and associated externalizing behaviors). Dr. Chester will also be co-mentored by Dr. David Goldman (an expert on the genetic and neural basis of alcohol misuse and associated externalizing behaviors), Dr. Fazil Aliev (an expert in statistical genetics), Dr. Dominic Parrot (an expert in alcohol-influenced aggression), and Dr. F. Gerard Moeller (an expert in the neural basis of alcohol misuse and associated externalizing behaviors). Research plan: The scientific objective of this K01 proposal is to examine the genetic factors that predispose certain individuals to act aggressively in the context of alcohol misuse. Further, we plan to investigate the neural mechanisms that link these genetic risk factors to actual acts of alcohol-influenced aggression. Genetic risk factors for alcohol-influenced aggression will be tested by analyzing existing data from [five NIH-funded publicly-available genomic datasets] and a new sample collected from VCU's NIAAA-funded Spit4Science project, which investigates longitudinal alcohol misuse trajectories among undergraduates. To investigate neural mechanisms, a sub-sample of the Spit4Science participants will be recruited for a study that will combine a placebo-controlled alcohol administration, laboratory aggression measures, and functional brain imaging (fMRI). This proposed research is the first systematic investigation of the genetic underpinnings of alcohol-influenced aggression, a serious threat to public health. Further, this can identify the neural pathways of these genetic effects, which can inform psychological and pharmacological interventions that may prove fruitful in reducing the violent consequences of alcohol misuse. This award would support these goals and advance NIAAA's strategic plan to identify mechanisms underlying alcohol misuse and subsequent recovery.